Ginsenoside Rg1 Regulates the Activation of Astrocytes Through lncRNA-Malat1/miR-124-3p/Lamc1 Axis Driving PI3K/AKT Signaling Pathway, Promoting the Repair of Spinal Cord Injury

IF 4.8 1区 医学 Q1 NEUROSCIENCES CNS Neuroscience & Therapeutics Pub Date : 2024-11-03 DOI:10.1111/cns.70103
Yin Zhu, Wenjun Zou, Baihan Sun, Kelv Shen, Feiyun Xia, Hao Wang, Fengxian Jiang, Zhengfeng Lu
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Abstract

Aim

To investigate the regulation of ginsenoside Rg1 on the PI3K/AKT pathway through the lncRNA-Malat1/miR-124-3p/ Laminin gamma1 (Lamc1) axis, activating astrocytes (As) to promote the repair of spinal cord injury (SCI).

Methods

Bioinformatics analysis was used to predict miRNA targeting Lamc1 and lncRNA targeting miR-124-3p, which were then validated through a dual-luciferase assay. Following transfection, the relationships between Malat1, miR-124-3p, and Lamc1 expression levels were assessed by qRT-PCR and Western blot (WB). Immunofluorescence staining and immunohistochemistry were utilized to measure Lamc1 expression, while changes in cavity area were observed through hematoxylin–eosin (HE) staining. Basso-Beattie-Bresnahan (BBB) scale and footprint analysis were used to evaluate functional recovery. WB was performed to assess the expression of PI3K/AKT pathway-related protein.

Results

Rg1 was found to upregulate Malat1 expression, which in turn modulated the Malat1/miR-124-3p/Lamc1 axis. Furthermore, Rg1 activated the PI3K/Akt signaling pathway, significantly reducing the SCI cavity area and improving hind limb motor function. However, knockout of Malat1 hindered these effects, and inhibition of miR-124-3p reversed the silencing effects of Malat1.

Conclusions

Rg1 can induce Malat1 expression to activate the Lamc1/PI3K/AKT signaling pathway by sponging with miR-124-3p, thereby regulating As activity to repair SCI.

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人参皂苷Rg1通过lncRNA-Malat1/miR-124-3p/Lamc1轴驱动PI3K/AKT信号通路调控星形胶质细胞的激活,促进脊髓损伤的修复
目的:研究人参皂苷Rg1通过lncRNA-Malat1/miR-124-3p/ Laminin gamma1(Lamc1)轴调控PI3K/AKT通路,激活星形胶质细胞(As)促进脊髓损伤(SCI)修复:方法:利用生物信息学分析预测靶向Lamc1的miRNA和靶向miR-124-3p的lncRNA,然后通过双荧光素酶试验进行验证。转染后,通过 qRT-PCR 和 Western 印迹(WB)评估 Malat1、miR-124-3p 和 Lamc1 表达水平之间的关系。免疫荧光染色和免疫组化被用来测量Lamc1的表达,而空腔面积的变化则通过苏木精-伊红(HE)染色来观察。巴索-巴蒂-布雷斯纳汉(BBB)量表和足迹分析用于评估功能恢复情况。进行WB检测以评估PI3K/AKT通路相关蛋白的表达:结果:研究发现,Rg1能上调Malat1的表达,进而调节Malat1/miR-124-3p/Lamc1轴。此外,Rg1还能激活PI3K/Akt信号通路,显著减少SCI腔面积并改善后肢运动功能。然而,Malat1的敲除阻碍了这些效应,而miR-124-3p的抑制则逆转了Malat1的沉默效应:结论:Rg1能诱导Malat1的表达,通过与miR-124-3p的海绵作用激活Lamc1/PI3K/AKT信号通路,从而调节As的活性以修复SCI。
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来源期刊
CNS Neuroscience & Therapeutics
CNS Neuroscience & Therapeutics 医学-神经科学
CiteScore
7.30
自引率
12.70%
发文量
240
审稿时长
2 months
期刊介绍: CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.
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